Switching roles: the functional plasticity of adult tissue stem cells.

Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles.We thank J. Fowler, J. Frede, P. Greulich, A.M. Klein, K. Murai, B.D. Simons and D.J. Winton for discussions. We acknowledge the support of the Medical Research Council, the Wellcome Trust (Project grant WT090334MA, P.H.J. and PhD studentship Programme in Stem Cell Biology & Medicine, A.W.) and Cancer Research UK (Programme Grant C609/A17257, P.H.J.).This is the author accepted manuscript. The final version is available via EMBO at http://emboj.embopress.org/content/34/9/1164.long#ack-1

Case of a sigmoid colon cancer with metachronous metastases to the mesorectum and the abdominal wall

<p>Abstract</p> <p>Backround</p> <p>Sigmoid colon cancer metachronous metastases commonly occur in the liver and lungs with sporadic reports also to the spleen, stomach, thyroid gland, abdominal wall and upper urinary tract. This is a rare case of metachronous metastases invading the mesorectum and the abdominal wall.</p> <p>Case presentation</p> <p>A 72-year-old female underwent sigmoidectomy for stage I (T2N0 M0) sigmoid colon cancer in May 2008. In June 2009, an abdominal computed tomography scan revealed a tumor 2 cm in size at the lower anterior mesorectum and a second mass 2 cm in size at the anterior abdominal wall midline. Total colonoscopy showed no mucosal lesion. The serum carcinoembryonic antigen level was normal. A biopsy of the mesorectum tumor showed similar histologic characteristics with the primary tumor. Since no other site of recurrence was identified, an abdominoperineal resection was attempted. During the operation and after the removal of the incision recurrence, sinus bradycardia and signs of myocardial ischemia were noticed. A loop transverse colostomy was immediately perfomed and the operation was terminated. Postoperative cardiologic examination revealed an acute myocardium infract. Chemo-radiation of the mesorectum tumor and re-evaluation for surgical excision was decided.</p> <p>Conclusion</p> <p>Metachronous metastasis of the mesorectum from sigmoid colon cancer is extremely rare. Although patterns of lymphatic spread from rectal cancer to sigmoid colon have recently been demonstrated, there is no evidence of metachronous mesorectum invasion from sigmoid colon cancer. This could be the issue for future trials.</p

Logics of Finite Hankel Rank

We discuss the Feferman-Vaught Theorem in the setting of abstract model theory for finite structures. We look at sum-like and product-like binary operations on finite structures and their Hankel matrices. We show the connection between Hankel matrices and the Feferman-Vaught Theorem. The largest logic known to satisfy a Feferman-Vaught Theorem for product-like operations is CFOL, first order logic with modular counting quantifiers. For sum-like operations it is CMSOL, the corresponding monadic second order logic. We discuss whether there are maximal logics satisfying Feferman-Vaught Theorems for finite structures.Comment: Appeared in YuriFest 2015, held in honor of Yuri Gurevich's 75th birthday. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-23534-9_1

Moving Your Sons to Safety: Galls Containing Male Fig Wasps Expand into the Centre of Figs, Away From Enemies

Figs are the inflorescences of fig trees (Ficus spp., Moraceae). They are shaped like a hollow ball, lined on their inner surface by numerous tiny female flowers. Pollination is carried out by host-specific fig wasps (Agaonidae). Female pollinators enter the figs through a narrow entrance gate and once inside can walk around on a platform generated by the stigmas of the flowers. They lay their eggs into the ovules, via the stigmas and styles, and also gall the flowers, causing the ovules to expand and their pedicels to elongate. A single pollinator larva develops in each galled ovule. Numerous species of non-pollinating fig wasps (NPFW, belonging to other families of Chalcidoidea) also make use of galled ovules in the figs. Some initiate galls, others make use of pollinator-generated galls, killing pollinator larvae. Most NPFW oviposit from the outside of figs, making peripherally-located pollinator larvae more prone to attack. Style length variation is high among monoecious Ficus spp. and pollinators mainly oviposit into more centrally-located ovules, with shorter styles. Style length variation is lower in male (wasp-producing) figs of dioecious Ficus spp., making ovules equally vulnerable to attack by NPFW at the time that pollinators oviposit

A study of lymph node ratio in stage IV colorectal cancer

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: The finding of metastasis in colorectal cancer, stage IV disease, has a major impact on prognosis and treatment strategy. Known important factors include the extent of the metastasis and the patients &apos; performance status. The lymph node factors are of known importance in earlier cancer stages but less described in metastatic disease. The aim of the study was to evaluate lymph node status and ratio as prognostic markers in stage IV colorectal cancer. Methods: The study was retrospective and assessing all patients operated, with bowel resection, for an initial stage IV colorectal cancer during 1999–2003 (n = 136). Basic demographic data as well as given treatment was assessed. The Lymph node ratio (LNR), the quota between the number of lymph node metastasis and assessed lymph nodes, was calculated. LNR groups were created by ratio thirds, 3 equally sized groups. The analysis was made by LNR group and by eligibility for chemotherapy with cancer specific survival as outcome parameter. Results: The median survival (CSS) for the entire group was 431 days with great variability. For the patients eligible for chemotherapy it ranged from 791 days in LNR-group 1 to 433 days for th

Survival endpoints in colorectal cancer and the effect of second primary other cancer on disease free survival

<p>Abstract</p> <p>Background</p> <p>In cancer research the selection and definitions of survival endpoints are important and yet they are not used consistently. The aim of this study was to compare different survival endpoints in patients with primary colorectal cancer (CRC) and to understand the effect of second primary other cancer on disease-free survival (DFS) calculations.</p> <p>Methods</p> <p>A population-based cohort of 415 patients with CRC, 332 of whom were treated with curative intention between the years 2000-2003, was analysed. Events such as locoregional recurrence, distant metastases, second primary cancers, death, cause of death and loss to follow-up were recorded. Different survival endpoints, including DFS, overall survival, cancer-specific survival, relapse-free survival, time to treatment failure and time to recurrence were compared and DFS was calculated with and without inclusion of second primary other cancers.</p> <p>Results</p> <p>The events that occurred most often in patients treated with curative intention were non-cancer-related death (n = 74), distant metastases (n = 66) and death from CRC (n = 59). DFS was the survival endpoint with most events (n = 170) followed by overall survival (n = 144) and relapse-free survival (n = 139). Fewer events were seen for time to treatment failure (n = 80), time to recurrence (n = 68) and cancer-specific survival (n = 59). Second primary other cancer occurred in 26 patients and its inclusion as an event in DFS calculations had a detrimental effect on the survival. The DFS for patients with stage I-III disease was 62% after 5 years if second primary other cancer was not included as an event, compared with 58% if it was. However, the difference was larger for stage II (68 vs 60%) than for stage III (49 vs 47%).</p> <p>Conclusions</p> <p>The inclusion of second primary other cancer as an endpoint in DFS analyses significantly alters the DFS for patients with CRC. Researchers and journals must clearly define survival endpoints in all trial protocols and published manuscripts.</p

Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy

The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5–29.2%) and 49% (95% CI, 42.2–55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27–3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05–2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites ⩾2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation